Venous Thromboembolic Event (VTE) Prophylaxis in Medically Ill Patients (MAGELLAN)

This study has been completed.
Sponsor:
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00571649
First received: December 11, 2007
Last updated: June 3, 2014
Last verified: June 2014
Results First Received: February 16, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition: Venous Thromboembolism
Interventions: Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Enoxaparin
Drug: Rivaroxaban placebo
Drug: Enoxaparin placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First patient first visit date: 04 DEC 2007; last patient last visit date 24 NOV 2010. Primary completion date: 12 AUG 2010. Participants were aged ≥40 years, hospitalized for an acute medical illness, and at risk of Venous Thromboembolism (VTE) (with heart failure, cancer, ischemic stroke, infection or inflammation, or respiratory insufficiency)

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 8428 participants were screened; 327 failed. 8101 were randomized. 7998 (98.7%) were in the Safety Analysis Set (SAF), i.e. received study medication. 6024 (74.4%) were in the modified Intent to Treat (at Day 35) group (valid for SAF with adequate assessment of venous thromboembolism). A total of 6005 (74.1%) completed study.

Reporting Groups
  Description
Rivaroxaban (Xarelto, BAY59-7939) Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days during treatment period
Enoxaparin Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days during treatment period

Participant Flow for 2 periods

Period 1:   Treatment Period
    Rivaroxaban (Xarelto, BAY59-7939)     Enoxaparin  
STARTED     4050     4051  
Participants Received Treatment     3997     4001  
Day 10     3454     3499  
Day 35     3033     3115  
COMPLETED     2958     3047  
NOT COMPLETED     1092     1004  
Adverse Event                 438                 385  
Clinical endpoint reached                 50                 56  
Withdrawal by Subject                 285                 255  
Death                 76                 59  
Physician Decision                 8                 9  
Lost to Follow-up                 43                 41  
Non-compliant with study medication                 88                 89  
Patient convenience                 11                 13  
Protocol Violation                 90                 92  
Technical problems                 3                 5  

Period 2:   Follow-up Period
    Rivaroxaban (Xarelto, BAY59-7939)     Enoxaparin  
STARTED     3583 [1]   3635 [1]
COMPLETED     3038 [2]   3107 [2]
NOT COMPLETED     545     528  
Adverse Event                 46                 40  
Clinical endpoint reached                 5                 2  
Withdrawal by Subject                 119                 115  
Death                 132                 133  
Physician Decision                 7                 13  
Lost to Follow-up                 95                 92  
Patient convenience                 136                 121  
Protocol Violation                 5                 12  
[1] Participants were required to enter follow-up even if treatment period not completed.
[2] Began day after last dose study drug; ended on Day 90 (+/- 7 days) .



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Rivaroxaban (Xarelto, BAY59-7939) Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days (SAF population)
Enoxaparin Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days (SAF population)
Total Total of all reporting groups

Baseline Measures
    Rivaroxaban (Xarelto, BAY59-7939)     Enoxaparin     Total  
Number of Participants  
[units: participants]
  3997     4001     7998  
Age  
[units: years]
Mean ± Standard Deviation
  69.2  ± 11.9     69.2  ± 11.7     69.2  ± 11.8  
Age, Customized  
[units: participants]
     
< 65 years     1323     1363     2686  
65 to < 75 years     1144     1090     2234  
>= 75 years     1530     1548     3078  
Gender  
[units: participants]
     
Female     1774     1898     3672  
Male     2223     2103     4326  
Race  
[units: participants]
     
White     2749     2744     5493  
Black     89     92     181  
Asian     793     794     1587  
Native American     12     12     24  
Hispanic     69     70     139  
Uncodable     106     112     218  
Unknown     1     0     1  
Missing     178     177     355  
Reason for hospitalization [1]
[units: participants]
     
Heart failure (NYHA Class III or NYHA Class IV)     1292     1301     2593  
Active cancer     294     290     584  
Acute ischemic stroke     691     692     1383  
Acute Infectious and Inflammatory Diseases     1904     1876     3780  
Acute infectious disease     1826     1801     3627  
Acute inflammatory or rheumatic disease     150     149     299  
Acute respiratory insufficiency     1085     1151     2236  
[1] Participants may have more than one acute condition as hospitalization reason. Acute medical illnesses included heart failure (New York Heart Association [NYHA] Class III [marked limitation of physical activity] or NYHA Class IV [inability to carry out any physical activity without discomfort)] active cancer, acute ischemic stroke, acute infectious and inflammatory diseases (including acute rheumatic diseases), acute respiratory insufficiency.



  Outcome Measures
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1.  Primary:   Percentage of Participants With Composite Endpoint of Venous Thromboembolism [VTE] (Any Deep Vein Thrombosis [DVT], Non Fatal Pulmonary Embolism [PE]) and VTE-related Death up to Day 35 + 6 Days   [ Time Frame: Up to Day 35 + 6 days ]

2.  Primary:   Percentage of Participants With Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 10 + 5 Days   [ Time Frame: Up to Day 10 + 5 days ]

3.  Secondary:   Percentage of Participants With Composite Endpoint of VTE (Any DVT, Non Fatal PE) and All-cause Mortality up to Day 35 + 6 Days   [ Time Frame: Up to Day 35 + 6 days ]

4.  Secondary:   Percentage of Participants With Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 10 + 5 Days Per mITT Population   [ Time Frame: Up to Day 10 + 5 days ]

5.  Secondary:   Percentage of Participants With VTE Combined With All-cause Mortality up to Day 10 + 5 Days   [ Time Frame: Up to Day 10 + 5 days ]

6.  Secondary:   Percentage of Participants With Symptomatic VTE, Including and Excluding VTE-related Death up to Days 10, 35, and 90   [ Time Frame: At Day 10 + 5 days, at Day 35 + 6 days, and at Day 90 + 7 days ]

7.  Secondary:   Percentage of Participants With Net Clinical Benefit (Any DVT, Non-fatal PE, VTE-related Death, Plus Major and Clinically Relevant Non-major Bleeding Events) up to Day 35 + 6 Days   [ Time Frame: Up to Day 35 + 6 days ]

8.  Secondary:   Percentage of Participants With Net Clinical Benefit (Any DVT, Non-fatal PE, VTE-related Death, Plus Major and Clinically Relevant Non-major Bleeding Events) up to Day 10 + 5 Days   [ Time Frame: Up to Day 10 + 5 days ]

9.  Secondary:   Percentage of Participants With Major Vascular Events up to Days 10, 35, and 90   [ Time Frame: At Day 10 + 5 days, at Day 35 + 6 days, and at Day 90 + 7 days ]

10.  Secondary:   Percentage of Participants With Each Component of the Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 35 + 6 Days   [ Time Frame: Up to Day 35 + 6 days ]

11.  Secondary:   Percentage of Participants With Each Component of the Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 10 + 5 Days   [ Time Frame: Up to Day 10 + 5 days ]

12.  Secondary:   Percentage of Participants With All-cause Mortality up to Day 90 + 7 Days   [ Time Frame: Up to Day 90 + 7 days ]

13.  Secondary:   Percentage of Participants With the Composite of Treatment Emergent Major Bleeding Events and Non-major Clinically Relevant Bleeding Events up to 2 Days After Last Intake of Any Study Medication (Day 35 + 6 Days)   [ Time Frame: Up to Day 35 + 6 days ]

14.  Secondary:   Percentage of Participants With the Composite of Treatment Emergent Major Bleeding Events and Non-major Clinically Relevant Bleeding Events up to 2 Days After Last Application of a Study Medication Syringe (Day 10 + 5 Days)   [ Time Frame: Up to Day 10 + 5 days ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   0.5%  

Reporting Groups
  Description
Rivaroxaban (Xarelto, BAY59-7939) Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days
Enoxaparin Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days

Other Adverse Events
    Rivaroxaban (Xarelto, BAY59-7939)     Enoxaparin  
Total, other (not including serious) adverse events      
# participants affected / at risk     2297/3997     2291/4001  
Blood and lymphatic system disorders      
Anaemia * 1    
# participants affected / at risk     87/3997 (2.18%)     85/4001 (2.12%)  
# events     93     87  
Neutropenia * 1    
# participants affected / at risk     20/3997 (0.50%)     16/4001 (0.40%)  
# events     32     20  
Thrombocytopenia * 1    
# participants affected / at risk     29/3997 (0.73%)     25/4001 (0.62%)  
# events     32     27  
Cardiac disorders      
Atrial fibrillation * 1    
# participants affected / at risk     74/3997 (1.85%)     61/4001 (1.52%)  
# events     82     65  
Cardiac failure * 1    
# participants affected / at risk     43/3997 (1.08%)     38/4001 (0.95%)  
# events     46     44  
Mitral valve incompetence * 1    
# participants affected / at risk     36/3997 (0.90%)     32/4001 (0.80%)  
# events     36     33  
Tachycardia * 1    
# participants affected / at risk     32/3997 (0.80%)     43/4001 (1.07%)  
# events     33     49  
Tricuspid valve incompetence * 1    
# participants affected / at risk     19/3997 (0.48%)     22/4001 (0.55%)  
# events     19     22  
Ventricular extrasystoles * 1    
# participants affected / at risk     24/3997 (0.60%)     17/4001 (0.42%)  
# events     26     17  
Ear and labyrinth disorders      
Vertigo * 1    
# participants affected / at risk     26/3997 (0.65%)     25/4001 (0.62%)  
# events     26     26  
Eye disorders      
Conjunctivitis * 1    
# participants affected / at risk     16/3997 (0.40%)     24/4001 (0.60%)  
# events     16     24  
Gastrointestinal disorders      
Abdominal pain * 1    
# participants affected / at risk     89/3997 (2.23%)     56/4001 (1.40%)  
# events     109     64  
Abdominal pain upper * 1    
# participants affected / at risk     59/3997 (1.48%)     53/4001 (1.32%)  
# events     63     62  
Constipation * 1    
# participants affected / at risk     362/3997 (9.06%)     346/4001 (8.65%)  
# events     418     375  
Diarrhoea * 1    
# participants affected / at risk     214/3997 (5.35%)     230/4001 (5.75%)  
# events     238     256  
Dyspepsia * 1    
# participants affected / at risk     53/3997 (1.33%)     62/4001 (1.55%)  
# events     54     69  
Gastritis * 1    
# participants affected / at risk     36/3997 (0.90%)     38/4001 (0.95%)  
# events     37     38  
Gastritis erosive * 1    
# participants affected / at risk     20/3997 (0.50%)     19/4001 (0.47%)  
# events     21     19  
Gingival bleeding * 1    
# participants affected / at risk     20/3997 (0.50%)     9/4001 (0.22%)  
# events     22     9  
Hiatus hernia * 1    
# participants affected / at risk     20/3997 (0.50%)     16/4001 (0.40%)  
# events     20     16  
Nausea * 1    
# participants affected / at risk     207/3997 (5.18%)     226/4001 (5.65%)  
# events     242     253  
Vomiting * 1    
# participants affected / at risk     170/3997 (4.25%)     149/4001 (3.72%)  
# events     205     175  
Haemorrhoidal haemorrhage * 1    
# participants affected / at risk     22/3997 (0.55%)     12/4001 (0.30%)  
# events     23     12  
General disorders      
Asthenia * 1    
# participants affected / at risk     52/3997 (1.30%)     31/4001 (0.77%)  
# events     54     32  
Chest pain * 1    
# participants affected / at risk     89/3997 (2.23%)     77/4001 (1.92%)  
# events     102     82  
Fatigue * 1    
# participants affected / at risk     33/3997 (0.83%)     35/4001 (0.87%)  
# events     35     35  
Injection site haemorrhage * 1    
# participants affected / at risk     8/3997 (0.20%)     21/4001 (0.52%)  
# events     8     23  
Oedema peripheral * 1    
# participants affected / at risk     132/3997 (3.30%)     115/4001 (2.87%)  
# events     153     127  
Pain * 1    
# participants affected / at risk     42/3997 (1.05%)     39/4001 (0.97%)  
# events     46     40  
Pyrexia * 1    
# participants affected / at risk     132/3997 (3.30%)     131/4001 (3.27%)  
# events     158     162  
Hepatobiliary disorders      
Cholelithiasis * 1    
# participants affected / at risk     49/3997 (1.23%)     47/4001 (1.17%)  
# events     50     48  
Hepatic function abnormal * 1    
# participants affected / at risk     17/3997 (0.43%)     24/4001 (0.60%)  
# events     18     24  
Hepatic steatosis * 1    
# participants affected / at risk     48/3997 (1.20%)     61/4001 (1.52%)  
# events     48     61  
Infections and infestations      
Bronchitis * 1    
# participants affected / at risk     64/3997 (1.60%)     47/4001 (1.17%)  
# events     65     48  
Cellulitis * 1    
# participants affected / at risk     22/3997 (0.55%)     18/4001 (0.45%)  
# events     22     19  
Nasopharyngitis * 1    
# participants affected / at risk     37/3997 (0.93%)     36/4001 (0.90%)  
# events     38     36  
Oral candidiasis * 1    
# participants affected / at risk     31/3997 (0.78%)     34/4001 (0.85%)  
# events     31     35  
Pneumonia * 1    
# participants affected / at risk     73/3997 (1.83%)     65/4001 (1.62%)  
# events     75     68  
Upper respiratory tract infection * 1    
# participants affected / at risk     30/3997 (0.75%)     26/4001 (0.65%)  
# events     33     27  
Urinary tract infection * 1    
# participants affected / at risk     138/3997 (3.45%)     142/4001 (3.55%)  
# events     148     151  
Injury, poisoning and procedural complications      
Fall * 1    
# participants affected / at risk     33/3997 (0.83%)     40/4001 (1.00%)  
# events     38     40  
Contusion * 1    
# participants affected / at risk     38/3997 (0.95%)     42/4001 (1.05%)  
# events     50     63  
Investigations      
Alanine aminotransferase increased * 1    
# participants affected / at risk     32/3997 (0.80%)     61/4001 (1.52%)  
# events     32     66  
Aspartate aminotransferase increased * 1    
# participants affected / at risk     23/3997 (0.58%)     35/4001 (0.87%)  
# events     23     36  
Blood creatinine increased * 1    
# participants affected / at risk     38/3997 (0.95%)     36/4001 (0.90%)  
# events     40     39  
Blood urea increased * 1    
# participants affected / at risk     24/3997 (0.60%)     23/4001 (0.57%)  
# events     27     24  
Creatinine renal clearance decreased * 1    
# participants affected / at risk     36/3997 (0.90%)     35/4001 (0.87%)  
# events     40     35  
Gamma-glutamyltransferase increased * 1    
# participants affected / at risk     31/3997 (0.78%)     32/4001 (0.80%)  
# events     31     32  
Haemoglobin decreased * 1    
# participants affected / at risk     23/3997 (0.58%)     12/4001 (0.30%)  
# events     26     12  
Metabolism and nutrition disorders      
Dehydration * 1    
# participants affected / at risk     43/3997 (1.08%)     30/4001 (0.75%)  
# events     49     30  
Diabetes mellitus * 1    
# participants affected / at risk     39/3997 (0.98%)     34/4001 (0.85%)  
# events     40     34  
Hyperglycaemia * 1    
# participants affected / at risk     46/3997 (1.15%)     50/4001 (1.25%)  
# events     54     63  
Hyperkalaemia * 1    
# participants affected / at risk     62/3997 (1.55%)     51/4001 (1.27%)  
# events     66     57  
Hypoglycaemia * 1    
# participants affected / at risk     37/3997 (0.93%)     39/4001 (0.97%)  
# events     46     48  
Hypokalaemia * 1    
# participants affected / at risk     191/3997 (4.78%)     184/4001 (4.60%)  
# events     219     219  
Hyponatraemia * 1    
# participants affected / at risk     35/3997 (0.88%)     34/4001 (0.85%)  
# events     38     34  
Decreased appetite * 1    
# participants affected / at risk     38/3997 (0.95%)     40/4001 (1.00%)  
# events     42     44  
Musculoskeletal and connective tissue disorders      
Arthralgia * 1    
# participants affected / at risk     62/3997 (1.55%)     76/4001 (1.90%)  
# events     68     87  
Back pain * 1    
# participants affected / at risk     97/3997 (2.43%)     82/4001 (2.05%)  
# events     105     85  
Muscle spasms * 1    
# participants affected / at risk     25/3997 (0.63%)     28/4001 (0.70%)  
# events     25     30  
Musculoskeletal pain * 1    
# participants affected / at risk     46/3997 (1.15%)     61/4001 (1.52%)  
# events     50     66  
Neck pain * 1    
# participants affected / at risk     14/3997 (0.35%)     22/4001 (0.55%)  
# events     14     25  
Osteoarthritis * 1    
# participants affected / at risk     29/3997 (0.73%)     22/4001 (0.55%)  
# events     30     24  
Pain in extremity * 1    
# participants affected / at risk     110/3997 (2.75%)     103/4001 (2.57%)  
# events     127     113  
Nervous system disorders      
Dizziness * 1    
# participants affected / at risk     81/3997 (2.03%)     72/4001 (1.80%)  
# events     83     80  
Headache * 1    
# participants affected / at risk     205/3997 (5.13%)     185/4001 (4.62%)  
# events     237     221  
Syncope * 1    
# participants affected / at risk     23/3997 (0.58%)     19/4001 (0.47%)  
# events     24     21  
Psychiatric disorders      
Anxiety * 1    
# participants affected / at risk     89/3997 (2.23%)     94/4001 (2.35%)  
# events     99     98  
Confusional state * 1    
# participants affected / at risk     28/3997 (0.70%)     23/4001 (0.57%)  
# events     28     24  
Depression * 1    
# participants affected / at risk     68/3997 (1.70%)     73/4001 (1.82%)  
# events     68     77  
Insomnia * 1    
# participants affected / at risk     172/3997 (4.30%)     185/4001 (4.62%)  
# events     199     202  
Sleep disorder * 1    
# participants affected / at risk     25/3997 (0.63%)     16/4001 (0.40%)  
# events     25     18  
Renal and urinary disorders      
Dysuria * 1    
# participants affected / at risk     22/3997 (0.55%)     15/4001 (0.37%)  
# events     23     15  
Haematuria * 1    
# participants affected / at risk     65/3997 (1.63%)     48/4001 (1.20%)  
# events     68     53  
Renal cyst * 1    
# participants affected / at risk     65/3997 (1.63%)     61/4001 (1.52%)  
# events     65     63  
Renal failure * 1    
# participants affected / at risk     52/3997 (1.30%)     47/4001 (1.17%)  
# events     55     48  
Renal failure acute * 1    
# participants affected / at risk     25/3997 (0.63%)     19/4001 (0.47%)  
# events     26     19  
Urinary retention * 1    
# participants affected / at risk     22/3997 (0.55%)     17/4001 (0.42%)  
# events     23     19  
Renal impairment * 1    
# participants affected / at risk     39/3997 (0.98%)     29/4001 (0.72%)  
# events     40     31  
Reproductive system and breast disorders      
Benign prostatic hyperplasia * 1    
# participants affected / at risk     44/3997 (1.10%)     20/4001 (0.50%)  
# events     45     20  
Respiratory, thoracic and mediastinal disorders      
Chronic obstructive pulmonary disease * 1    
# participants affected / at risk     71/3997 (1.78%)     59/4001 (1.47%)  
# events     92     84  
Cough * 1    
# participants affected / at risk     107/3997 (2.68%)     94/4001 (2.35%)  
# events     118     100  
Dyspnoea * 1    
# participants affected / at risk     107/3997 (2.68%)     99/4001 (2.47%)  
# events     120     112  
Epistaxis * 1    
# participants affected / at risk     123/3997 (3.08%)     66/4001 (1.65%)  
# events     145     83  
Haemoptysis * 1    
# participants affected / at risk     37/3997 (0.93%)     32/4001 (0.80%)  
# events     40     37  
Pleural effusion * 1    
# participants affected / at risk     28/3997 (0.70%)     31/4001 (0.77%)  
# events     32     32  
Oropharyngeal pain * 1    
# participants affected / at risk     27/3997 (0.68%)     27/4001 (0.67%)  
# events     28     28  
Skin and subcutaneous tissue disorders      
Decubitus ulcer * 1    
# participants affected / at risk     21/3997 (0.53%)     18/4001 (0.45%)  
# events     22     23  
Ecchymosis * 1    
# participants affected / at risk     42/3997 (1.05%)     39/4001 (0.97%)  
# events     47     42  
Erythema * 1    
# participants affected / at risk     27/3997 (0.68%)     37/4001 (0.92%)  
# events     30     41  
Pruritus * 1    
# participants affected / at risk     47/3997 (1.18%)     50/4001 (1.25%)  
# events     47     51  
Rash * 1    
# participants affected / at risk     41/3997 (1.03%)     50/4001 (1.25%)  
# events     44     51  
Vascular disorders      
Haematoma * 1    
# participants affected / at risk     24/3997 (0.60%)     24/4001 (0.60%)  
# events     29     26  
Hypertension * 1    
# participants affected / at risk     154/3997 (3.85%)     156/4001 (3.90%)  
# events     177     178  
Hypertensive crisis * 1    
# participants affected / at risk     20/3997 (0.50%)     16/4001 (0.40%)  
# events     23     18  
Hypotension * 1    
# participants affected / at risk     82/3997 (2.05%)     93/4001 (2.32%)  
# events     91     102  
Phlebitis * 1    
# participants affected / at risk     37/3997 (0.93%)     38/4001 (0.95%)  
# events     38     41  
Aortic arteriosclerosis * 1    
# participants affected / at risk     25/3997 (0.63%)     19/4001 (0.47%)  
# events     25     19  
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA (13.1)



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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
A heterogeneous population (with different acute medical illnesses and severity of illness) was included in the trial. VTE risk in acute medical illnesses is moderate [with no thromboprophylaxis] .


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